Substituted 1,3,5-triazinyl-(6)-aminophenyl-arsenic compounds



Patented Oct. 9, 1945 UNITED STA PATENT.

SUBSTITUTED 1,3,5-TRIAZINYL- (6)-AM]N0- PHENYL-ARSENIC COMPOUNDS Ernst A; H. Friedheim, New York, N.

i No Drawing. Application December 9, 1941, Se-

, rig] No. 422,234. In Switzerland December 10,

10 Claims. (01. 260-242) This invention relates to derivatives of triazines containing arsenic, and more particularly to triazine derivatives which contain trivalent arsenic.

In my U. S. Patent No. 2,295,574, issued on Sept. 15, 1942, I have shown that condensation of suitable derivatives of symmetric triazine with phenyl-arsonic acid derivatives results in a new type of condensation products possessing valuable therapeutic properties in diseases, caused by spirochaetes or trypanosomes, suchas syphilis, and African sleeping sickness. a m

I have found that new triazine derivatives containing arsenic can be obtained by condensing derivatives of 1,3,5-triazine of the formula with an aromatic organic compound containing trivalent arsenic and corresponding to the formulaW--CsHz(A,B)--As=X.

" In these formulas, W, is an amino-group or halogen. If W is an amino-group, at least one of the groups D, E, F is a halogen-group. If W is a halogen, at least one of the groups D, E, F is an amino-group. In both cases the othergroups are selected from the group consisting of halogen, NHz, NH alk., -N alk.2, hydroxy-alkyl-amino,

dialkyl-amino-alkyl-amino, and aminoacyl radicals, such as -NHCOCH3 and NHCOCsHsi it is to be understood that in the appended claims the term .amino radicals includes NHz radicals as well as the before mentioned substituted amino-radicals; the radicals A and B are selected from the [group consisting of. hydrogen; halogen,

The condensation products th'us' formedahave theformula 1 i J t A Y C CNH-,C6Hg(A,B),As X

wherein Y and Y areeach .a ,radicalfise from the group consisting of halogen, NH alk Nalk.2,hydroxy alkyl amino nonzcrioncnzon l dialkyl-amino-alkyl-arnino, and aminoa cyiradiicals; A and B are'selected from the'group con sisting of hydrogen; halogen, OH, O alk., O acyl N02, NHZ, NH a1k., N alka, amino-acyl, and a-llgyl radicals, and'X' is a divalent-radicalselected from theg'roup consisting of O, S, dihalides; sul fur-containing groups oft-the, type S' R. 2, wherein R is an organic radical which is capable of carrying an SH-'-- radical, and groups having theformula I i I In carrying out the present inventiom fo ex; ample, an aqueous solution ,containingone moi of 4 oxy-3-aminophehylarsiHQXidehray becaused toreact witha fine suspension oil mql offiglQiie trichloro,, ,3,5-triazine in watergat a temperature of 0 C.-With the exclusion mof oxy enlfi'I'he' re;- sulting condensation product has the formula Subsequently, this reaction product may be treated with a base selected from the group consisting of ammonia, alkyl amines, hydroXy-alkyl amines and dialkyl-aminoalkyLamines. Similar reactions may be obtained by usingja dihalide such as 4-amino-phenylarsindichlorideinstead of 4-oxy-3-amino-phenylarsinoxide. Instead of the latter, its derivatives orisomers, such as,for-in ture taking a yellow color.

triazine and a substituted phenyl-arsonic acid,

and converting the condensation product thus obtained, into a compound containing trivalent arsenic. I have found that suchconversion can be performed without the disintegrationof the basic triazinyl-aminobenzene structure by treating the triazinyl-aminobenzene-'arsonic acid condensation product in hydrochloric acid solution, in the presencelof hydriodic acid, with S02, hypophosphorous acid (I-IzPOs), r stannous chloride or in neutral or alkaline solution with phenylhydrazine or sodium hydrosulfite (NazSzOl). The reduction with S02 or phenylhydrazine leads to the arsinoxides, or dihalogenarsines, While the treatment with stannous chloride, hypophosphorous acid, and sodium hydrosulfite leads to the corresponding arseno-compounds.

For example, one part by weight of 2,4-diamino-1,3,5-tfiazinyl (6) [amino 3 oxy 4- phenylarsonic acid I]. is dissolvedat about 80 C.

derivative of 1 tioned copending application, p-[2,4-dichlorohydrochloric acid, and insoluble in ether and chloroform.

Other compounds according to my present invention may be obtained by applying the above described reduction processes to other arsonoanilino-triazine compounds, such as monochlormonoamino-arsono-anilino-triazine, and other arsono-anilino-triazine compounds obtained according to my above mentioned U. SJ Patent No. 2,295,574.

.As described in Example 2 of my above men- 7 1,3,5-triazinyl- (6) l-aminophenylarsonic acid may be treated with ammonia in order to convert it into a 2-chloro-4-amino compound by covering said dichloro-compound with 10 times the quantity of 10% aqueous ammonia, and shaking at in 100 parts of hydrochloric acid of sp. gr. 1.19.

To the clear, warm solution /50 part of sodium iodideis added, and a stream of S02 gas is allowed to pass through the solution. After a few minutes the solution becomes cloudy, and the hydrochloride of 2,4 diamino -l,3 5-triazinyl-(6) -oxyaminophenylarsindichloride separates out in crystalline form. 'It is soluble in ethyl alcohol from which it may be recrystallized. It is Slightly soluble in acetone, and insoluble in chlor'oform,-CCl4 and benzene. The corresponding arsinoxide is formed bythe action of alkali, such as dilute'ammonia or sodium bicarbonate on the arsi'ndichloride.

An arseno-compound can be obtained by the action of stannous chloride on 2,4diamino-triazinyl-(6) -[4-oxy- 3 -amino phenylarsonic acid I]. One part of the latter is suspended in parts of aqueous hydrochloric acid of 1.19 density containing about 50% stannous chloride, and 1% of hydriodic acid. On gentle warming the substance goes slowly intosolution, the reaction mix- It becomes cloudy; and on standing a yellow precipitate separates, which represents the hydrochloride of the his 2,2-4,4'-tetraaminotriaziny1 6 6'(3-3- diamino- 4-4-dioxyarseno-benzene) of the formula:

45 C. for 1 hour, whereby the product goes into completesolution. By heating the [2-ch1oro-4- amino-1,3,5-triazinyl-(6)l aminophenyl-arsonic compound in hydrochloric acid solution with S02, a compound having the formula:

IITHr-HOI p I l N r V may be obtained.

Iclaim: 1. 1,3,5-triazine derivative of the formula wherein at least one of Y and Y is an aminoradical, while the other is selected from the group consisting of halogen radicals and aminoradicals; A and Bare selected from the group consisting of hydrogen, halogen, OI-I,-O-a1kyl, -O -acyl and alkyl radicals, and X'- is a divalent radlcalselected from the group consisting of O,

S, and dihalides. a v

2. 1,3,5-triazine derivative of the formula whereinY and Y are amino radicals; A and B are selected from the group consisting of hydrogen, halogen, .OH, -O-alkyl, -O-acy1 and alkyl radicals, and X" is a divalentradical selected from the group. consistingof O, S, and dihalides. V f

3. p-(2,4-diamino-triazonyl-(6))- [4 oxy 3- amino-phenyldichlorarsin-Il of the formula 4. p-(2,4-diamino-triazony1 (6) [4 oxy-3- amino-phenylarsinoxide-I] of the formula 5. A process for the preparation of a 1,3,5-triazine derivative as claimed in claim 1, said process comprising subjecting in aqueous solution a 1,3,5-triazine derivative of the formula If q Y1(IJ\ /G-NH- I l Z N As=X' wherein at least one of Y and Y is an aminoradical while the other is selected from the group consisting of halogen radicals and amino-radicals; A and B are selected from the group consisting of hydrogen, halogen, OH, O-alkyl, O-aoyl, and alkyl radicals, and X is a divalent radical selected from the group consisting of O, S, and dihalides, said process comprising subjecting said triazine compound to the action of SO: in the presence of hydrochloric acid and hydriodic acid.

7. p-(2,4-diamino-triazonyl 6) [4 aminophenylarsinozdde-I] of the formula:

8. 1,3,5-triazine derivative of the formula IiIHa wherein A and B are selected from the group consisting of hydrogen, halogen, OH, 0 alkyl, 0 acyl, and alkyl radicals, and X is a divalent radical selected from the group consisting of O, S and dihalides. i

9. 1,3,5-triazine derivative of the formula wherein A and B are selected from the group consisting of hydrogen, halogen, OH, O-allgvl, O-acyl, and alkyl radicals.

ERNST A. H. FRIEDHEM 

